Samuel E. Stinnette

Race and Sex Differences in Antiretroviral Therapy Use and Mortality among HIV-Infected Persons in Care

BACKGROUND There are conflicting data regarding race, sex, and mortality among persons infected with human immunodeficiency virus (HIV). We studied all-cause mortality among persons in care during the highly-active antiretroviral therapy (HAART) era. METHODS This retrospective cohort study included patients who made>or=1 clinic visit from January 1998 through December 2005. RESULTS Of 2605 patients (with 6657 person-years of follow-up), 38% were black and 24% were female. The percentage of time in care while receiving HAART was lower for blacks than for nonblacks (47% vs. 76%; P<.001) and for females than for males (57% vs. 71%; P=.01). There were 253 deaths (38 per 1000 person-years). After adjustment for characteristics at baseline, death was associated with black race (hazard ratio [HR], 1.33; P .04), female sex (HR, 1.53; P .007), injection drug use (IDU) as a risk factor for HIV infection (HR, 1.61; P .009), older age (HR, 1.45 per 10 years; P<.001), a lower CD4 cell count (HR, 0.59 for 200 vs. 350 cells/mm3; P<.001) and a higher HIV type 1 RNA level (HR, 1.35; P<.001). After adjustment for the length of time that HAART was received, black race (HR, 1.00; P .99) and IDU (HR, 1.37; P .09) were no longer associated with death, but female sex was (HR, 1.62; P=.002). CONCLUSIONS Race-associated differences in mortality likely resulted from HAART use. Women had an increased risk of death even after adjustment for HAART use. Addressing racial disparities will require improved HAART utilization. Increased mortality among women requires further study.

An Optimal Body Mass Index Range Associated With Improved Immune Reconstitution Among HIV-Infected Adults Initiating Antiretroviral Therapy

BACKGROUND Higher body mass index (BMI) was associated with slower human immunodeficiency virus (HIV) disease progression before the availability of effective antiretroviral therapy (ART), but the relationship between pretreatment BMI and CD4(+) lymphocyte recovery on ART is not well described. METHODS We conducted an observational cohort study of HIV-infected, ART-naive adults starting treatment at a clinic affiliated with Vanderbilt University in Nashville, Tennessee. We assessed the relationship between pretreatment BMI and CD4(+) lymphocyte count change from baseline to 12 months in all subjects, among those with plasma HIV-1 RNA levels <400 copies/mL for ≥ 6 months and those with <10% change in weight during follow-up. Linear regression models were adjusted for age, sex, race, protease inhibitor usage, year of ART initiation, and baseline CD4(+) lymphocyte count and HIV-1 RNA level. RESULTS A total of 915 patients met inclusion criteria; 78% were male, and their median age, BMI, and CD4(+) lymphocyte count were 39 years, 24 kg/m², and 171 cells/μL, respectively. The CD4(+) lymphocyte increase at 12 months was greatest among patients with a pretreatment BMI of ~25-30 kg/m² and diminished above and below this range (P = .03). Similar patterns were observed in the subgroup analyses. Among patients with a pretreatment CD4(+) lymphocyte count < 200 cells/μL, a BMI of ~25 kg/m² was associated with the highest odds of reaching a CD4(+) lymphocyte count > 350 cells/μL at 12 months (P = .05). CONCLUSIONS 12-month immune reconstitution on ART was highest among patients commonly classified as overweight, suggesting there may be an optimal BMI range for immune recovery on ART.

Non-AIDS-defining events among HIV-1-infected adults receiving combination antiretroviral therapy in resource-replete versus resource-limited urban setting

Objective:To compare incidence and distribution of non-AIDS-defining events (NADEs) among HIV-1-infected adults receiving combination antiretroviral therapy (cART) in urban sub-Saharan African versus United States settings. Design:Retrospective cohort analysis of clinical trial and observational data. Methods:Compared crude and standardized (to US cohort by age and sex) NADE rates from two urban adult HIV-infected cART-initiating populations: a clinical trial cohort in Gaborone, Botswana (Botswana) and an observational cohort in Nashville, Tennessee (USA). Results:Crude NADE incidence rates were similar: 10.0 [95% confidence interval 6.3–15.9] per 1000 person-years in Botswana versus 12.4 [8.4–18.4] per 1000 person-years in the United States. However, after standardizing to an older, predominantly male US population, the overall NADE incidence rates were higher in Botswana [18.7 (8.3–33.1) per 1000 person-years]. Standardized rates differed most for cardiovascular events (8.4 versus 5.0 per 1000 person-years) and non-AIDS-defining malignancies (8.0 versus 0.5 per 1000 person-years) – both higher in Botswana. Conversely, hepatic NADE rates were higher in the United States (4.0 versus 0.0 per 1000 person-years), whereas renal NADE rates [3.0 per 1000 person-years (United States) versus 2.4 per 1000 person-years (Botswana)] were comparable. Conclusion:Crude NADE incidence rates were similar between cART-treated patients in a US observational cohort and a sub-Saharan African clinical trial. However, when standardized to the US cohort, overall NADE rates were higher in Botswana. NADEs appear to be a significant problem in our sub-Saharan African setting, and the monitoring, prevention, and treatment of NADEs should be a critical component of care in resource-limited settings.

Drug Use and Receipt of Highly Active Antiretroviral Therapy among HIV-Infected Persons in Two U.S. Clinic Cohorts

Objective Drug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN) and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD) between 1999 and 2005. Methods Participants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care. Results 1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45–0.84] and OR = 0.58, 95% CI: [0.46–0.73], respectively for CCC and JHU) and less time on HAART at JHU (0.70, [0.55–0.88]), but not statistically associated with time on HAART at CCC (0.78, [0.56–1.09]). NIDU was independently associated with decreased HAART receipt (0.62, [0.47–0.81]) and less time on HAART (0.66, [0.52–0.85]) at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period. Conclusions Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization.

Increased Detectability of Plasma HIV-1 RNA after Introduction of a New Assay and Altered Specimen-Processing Procedures

After changes to assay and specimen-processing methods, plasma human immunodeficiency virus type 1 (HIV-1) RNA was frequently detectable in patients who previously had well-suppressed HIV-1 RNA levels. This artifact is attributable to shipping frozen plasma in primary plasma preparation tubes and is not caused by the HIV-1 RNA detection assay; it can be avoided by shipping plasma in a secondary tube.

Race, Kidney Disease Progression, and Mortality Risk in HIV-Infected Persons

BACKGROUND AND OBJECTIVES The burden of HIV-associated chronic kidney disease (CKD) is growing in the United States, partially because of increased HIV-infection rates among African Americans. We determined the prevalence, incidence, and risk of rapid estimated GFR (eGFR) decline, ESRD, and death among HIV-infected (HIV+) African-American and non-African-American individuals cared for at the Comprehensive Care Center in Nashville, Tennessee, from January 1, 1998, through December 31, 2005. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Mixed effects, competing risks, and Poisson and Cox regression models were used to assess the risk of rapid eGFR decline (defined as ≥50% decrease in baseline eGFR), CKD5/ESRD, and death. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Confounders were adjusted with a propensity score that related patient characteristics to the probability of being African American. Mixed effects models compared the rate of rapid eGFR decline for HIV-infected African Americans and non-African Americans. RESULTS There were 2468 HIV-infected individuals in the study: 33% African American; 21% female. Among all patients, HIV-infected African Americans did not have a statistically significant increased risk for rapid eGFR decline compared with non-African Americans. However, African Americans had a significantly higher risk of ESRD and tended toward a higher risk of death. CONCLUSIONS HIV-infected African Americans did not have a statistically significant difference in the risk of eGFR decline when compared with HIV-infected non-African Americans. The findings in this study have potential public health significance.

The relationship between injection and noninjection drug use and HIV disease progression

BACKGROUND Injection drug use is associated with poor HIV outcomes even among persons receiving highly active antiretroviral therapy (HAART), but there are limited data on the relationship between noninjection drug use and HIV disease progression. METHODS We conducted an observational study of HIV-infected persons entering care between January 1, 1999, and December 31, 2004, with follow-up through December 31, 2005. RESULTS There were 1,712 persons in the study cohort: 262 with a history of injection drug use, 785 with a history of noninjection drug use, and 665 with no history of drug use; 56% were White, and 24% were females. Median follow-up was 2.1 years, 33% had HAART prior to first visit, 40% initiated first HAART during the study period, and 306 (17.9%) had an AIDS-defining event or died. Adjusting for gender, age, race, prior antiretroviral use, CD4 cell count, and HIV-1 RNA, patients with a history of injection drug use were more likely to advance to AIDS or death than nonusers (adjusted hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.43-2.70, p < .01). There was no statistically significant difference of disease progression between noninjection drug users and nonusers (HR = 1.19, 95% CI = 0.92-1.56, p = .19). An analysis among the subgroup who initiated their first HAART during the study period (n = 687) showed a similar pattern (injection drug users: HR = 1.83, 95% CI = 1.09-3.06, p = .02; noninjection drug users: HR = 1.21, 95% CI = 0.81-1.80, p = .35). Seventy-four patients had active injection drug use during the study period, 768 active noninjection drug use, and 870 no substance use. Analyses based on active drug use during the study period did not substantially differ from those based on history of drug use. CONCLUSIONS This study shows no relationship between noninjection drug use and HIV disease progression. This study is limited by using history of drug use and combining different types of drugs. Further studies ascertaining specific type and extent of noninjection drug use prospectively, and with longer follow-up, are needed.

Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV-1-Infected Women: Maternal Virologic, Immunologic, and Clinical Response

Background Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed. Methods We conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30). Results Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (−0.35 vs. 0.10 log10 copies/mL, P = 0.03 and 183.8 vs. −70.8 cells/mm3, P = 0.03, respectively) but similar to those initiating HAART before pregnancy (−0.32 log10 copies/mL, P = 0.96 and 155.8 cells/mm3, P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy (P = 0.01). There were no statistical differences in rates of HIV disease progression between groups. Conclusions HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

Active cocaine use is associated with lack of HIV-1 virologic suppression independent of nonadherence to antiretroviral therapy: use of a rapid screening tool during routine clinic visits.

Abstract Clarifying the relationship between illicit drug use and HIV-1 virologic suppression requires characterization of both illicit drug use activity and adherence to antiretroviral therapy (ART). We developed a rapid clinical questionnaire to assess prior 7-day illicit drug use and ART adherence in a cross-sectional study among 1777 HIV-infected persons in care. Of these, 76% were male, 35% were African-American, and 8% reported injection drug use as their probable route of HIV-1 infection. Questionnaire-reported frequencies of cocaine and marijuana use within the previous 7 days were 3.3% and 12.1%, respectively. Over three quarters (77.8%) of participants were on ART, of whom 69.7% had HIV-1 virologic suppression (HIV-1 RNA<48 copies/mL). Univariate analyses revealed that compared to no use, cocaine and marijuana use were both associated with missed ART doses (P<0.01). Multivariable logistic regression analysis adjusting for nonadherence demonstrated that cocaine use was independently associated with failing to achieve virologic suppression (adjusted odds ratio (aOR): 0.46; 95% confidence interval (95% CI): 0.22–0.98) but marijuana use was not (aOR: 1.08; 95% CI: 0.72–1.62). This result strengthens the evidence of a direct effect of cocaine on virologic control, independent of nonadherence to ART.

Postpartum Discontinuation of Antiretroviral Therapy and Risk of Maternal AIDS-Defining Events, Non-AIDS–Defining Events, and Mortality Among a Cohort of HIV-1–Infected Women in the United States

This retrospective cohort study of HIV-infected women receiving highly active antiretroviral therapy (HAART) while pregnant assessed the effect of postpartum HAART discontinuation on maternal AIDS-defining events (ADEs), non-AIDS-defining events (non-ADEs), and death 1997-2008 in Nashville, Tennessee. Cox proportional hazards models compared rates of ADE or all-cause death and non-ADE or all-cause death, and competing risks analyses compared rates of ADE or ADE-related death and non-ADE or non-ADE-related death across the groups. There were two groups: women who stopped HAART postpartum (discontinuation, n = 54) and women who continued HAART postpartum (continuation, n = 69). Fifty percent were African American, 40% had prior non-HAART antiretroviral therapy (ART) use, and 38% had a history of illicit drug use. Median age was 27.5 years, baseline CD4(%) was 532 (34%) and CD4 nadir was 332 cells/mm(3), baseline and peak HIV-1 RNA were 2.6 and 4.32 log(10) copies per milliliter, respectively. Women in the continuation group were older, had lower baseline CD4, CD4%, and CD4 nadir, and had higher peak HIV-1 RNA. In multivariable proportional hazards models, the hazard ratios [95% confidence interval (CI)] of ADE or all-cause death and non-ADE or all-cause death were lower in the continuation group, but not statistically significantly: 0.50 (0.12, 2.12; p = 0.35) and 0.69 (0.24, 1.95; p = 0.48), respectively. The results were similar in competing risks analyses. Despite having characteristics associated with worse prognosis, women who continued HAART postpartum had lower hazard ratio point estimates for ADEs or death and non-ADEs or death than women who discontinued HAART. Larger studies with longer follow-up are indicated to assess this association.